Clinical Features and Outcome of Guillain-Barré Syndrome in Children.

Objective There are no reports about the clinical presentations and outcome of Guillain-Barré syndrome (GBS) in our region, therefore, we aimed to report some mentioned findings in children diagnosed with GBS in Isfahan, central Iran. Materials & Methods In this retrospective study, pediatric diagnosed with GBS referred to Imam Hossein Hospital, the Pediatric Referral Center of Isfahan Province, central Iran were enrolled from 2011-2014. The following data were extracted from the medical files of patients; age, gender, early signs and symptoms of GBS, neurological features, sensory and motor and autonomic involvements, sphincter dysfunction, bulbar muscle involvement, respiratory failure, cranial nerve paralysis, delay time from onset to definite diagnosis and management of GBS and the outcome. Results Overall, 57 children with GBS aged 1-13 yr were evaluated. Frequency of GBS was significantly higher in boys than in girls (38.6% vs. 61.4%, P=0.01, OR=0.39). The most common clinical presentations were distal lower limb weakness (92.11%), reduced deep tendon reflex (DTR) (82.46%) and neuropathic pain (75.44%). 92.9% of patients had complete recovery. Conclusion Distal lower limb weakness, reduced deep tendon reflex, and neuropathic pain are the main clinical presentation in children with GBS but in some patients, DTR may be normal or even exaggerated in early stage of disease. Revising the diagnostic criteria for GBS may be necessary. Most of our patients had complete recovery. The only death was due to autonomic involvement. Autonomic dysfunction could be associated with catastrophic outcome and patients with these clinical presentations need critical care.


Introduction
The Guillain-Barré syndrome (GBS) is an acute immune-mediated polyneuropathy considered as the most common causes of acute flaccid paralysis in healthy children (1,2). An overall worldwide incidence rate of GBS has been reported as 1 to 2 per 100000 per year (3). The rate ranges from 1.5 to 3.4 per 100000 among Iranian population (4). Although the syndrome could occur in all age groups, it predominantly affects adult population. GBS is more frequent in children aged 1-5 yr.
The syndrome is more prevalent among males than females (5, 6). GBS is thought to be an autoimmune disorder that results from T and B cell activated immune response to some preceding infectious agents such as Campylobacter jejuni, Cytomegalovirus, Epstein-Barr virus, Mycoplasma pneumoniae and HIV (7,8). Due to molecular mimicry of such infections, they to walk (10)(11)(12).
Understanding the clinical presentation as well as epidemiology of GBS in each population could help us in better understanding of the pathogenesis of the disease, its risk factors, and prognosis (13).
Moreover, evaluating the outcome of GBD could be effective in determining the disease-related morbidity and mortality and planning appropriate therapeutic plans.
There are no reports in this regard from Isfahan, central Iran, so we aimed to report clinical findings and outcome of children diagnosed with GBS from there.

Materials & Methods
In this retrospective study, pediatric patients    GBS was more prevalent among children aged less than 10 yr old (P<0.001, OR=27.19). The most and categorical variables were presented as mean (SD) and n (%), respectively. The continuous and categorical variables between and within studied groups were compared using Student's t-test and Chi-square test, respectively. The level of statistical significance was set at P<0.05.

Results
Overall, 57 children with GBS within the age Clinical Features and Outcome of Guillain-Barré Syndrome in Children  In our study, most of the patients were aged less than 10 yr old. Though patients in the 6-9 yr age group were higher than those aged less than 5 yr old, the difference was not significant. Some The most common clinical presentations were distal lower limb weakness, reduced deep tendon reflex, and neuropathic pain, similar to another study (21), and those reported in Mashhad, Tabriz, and Tehran in Iran (4,19,20).
The proportion of children with atypical clinical presentation of GBS was high with a rate of 24.2% (19).
In previous studies in Japan and Singapore, 13% and 10% of the patients with GBS had normal or increased DTR respectively (22,23). In our study, Reported range for cranial nerve involvement is 30%-46% (4,21,24). In our study, 26.3% of patients had cranial nerve involvement, bulbar weakness, followed by facial nerve and trigeminal palsy.
Our reported rate of cranial nerve palsy was similar to that reported in Korea (25), India (17) and Iran (19). It was lower than that of Tabriz (4) and Mashhad (21), but was higher than that of France (18).
The feature of cranial nerve palsy with predominance of bulbar nerve followed by facial nerve was similar to that reported in Mashhad (24) and Tabriz (4). Most studies reported that the involvement of facial nerve was more common than others (26).
Autonomic dysfunction is mainly manifested as abnormal sweating, sinus tachycardia, blood pressure instability, and pupillary abnormality (18). The frequency of autonomic dysfunction in our study was 8% that was lower than the rates reported by previous studies in both Iran and other countries (10,20). The outcome of one case with this presentation was death, the only death case among in our patients. He had tachycardia, abnormal sweating, and blood pressure instability.
The patient died due to recurrent uncontrollable cardiac arrhythmias.
The risk of respiratory muscles involvement requiring ventilatory support is lower in children than adults (27). In our study, 8% of patients received ventilator support because of respiratory insufficiency. The rate was reported to be 35%, 27%, 12% and 10.5% in India (17), Taiwan (28), France (18) and Tabriz (4), respectively. In a prospective multicenter study in Germany, 13% required artificial ventilation (29).
Sphincter dysfunction was reported in 5% of our studied population. The rate was 15.2% in the study in Tehran (19).
The prognosis of GBS in children is better than adults (18). In general, it has shorter clinical course with higher rate of complete recovery. Reported mortality rate for pediatrics GBS has been reported as 1%-2% (30). In this study, 92% of patients had complete recovery with a 1.8% mortality rate.
Our findings were similar to most of the reported studies in France (18), Tabriz (4) and India (17).
No death related to GBS was reported in Mashhad (20).
In this study, 5% of patients had incomplete recovery that was similar to that reported in India (17). The rate was lower than that reported (19) in Tehran with a rate of 27%. The main cause is higher rate of patients with a typical clinical presentation.
The limitations of this study were lower sample size and missing data regarding the antecedent illness preceding GBS. Results could be utilized as baseline data for better understanding of the characteristics of GBS in children and consequently better management of the disease as well as development of prognostic modeling score for our patients. It is also recommended to design prospective study in this field to achieve more results that are accurate.

Acknowledgement
We acknowledge the patients and their families who participated in this study.This study was conducted by financial support of Isfahan University of Medical Sciences.

Author`s Contribution
Jafar Nasiri contributed in conception of the work, conducting the study, revising the draft and agreed for all aspects of the work. MohamadReza Ghazavi contributed in conception of the work, conducting the study and agreed for all aspects of the work.
Omid Yaghini contributed in revising the draft and agreed for all aspects of the work. Mohammad Chaldavi contributed in conducting the study, writing the draft and agreed for all aspects of the work.
All authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.